title: Dose-dependent effects of hydralazine on microcirculatory function and hyperthermic response of murine FSall tumors.
abstract: The effects of the vasodilator hydralazine (HYD) on microcirculatory function and hyperthermic response were studied in early generation isotransplants of a spontaneous C3Hf/Sed mouse fibrosarcoma (FSall). Red blood cell flux (RBC flux) in superficial tumor regions was assessed using laser Doppler flowmetry. A differential microcirculatory response was seen between tumor and normal skin after 0.25 micrograms/g i.p. HYD, the tumor showing a transient increase in flow and the skin remaining almost stable. At 1.0 micrograms/g i.p., the differential response continued, this time with a transient fall in tumor blood flow but again no change in skin flow. High dose hydralazine (10.0 micrograms/g i.p.) was associated with a dramatic and prolonged decrease in tumor blood flow but a lesser and only transient decline in skin flow. Identical doses of hydralazine were given 30 min prior to heat treatment (43.5 degrees C for 15, 30, or 60 min). Tumor growth was measured daily and compared to controls (HT without hydralazine). Hydralazine at 0.25 micrograms/g i.p. did not affect heat induced growth delay. At 1.0 micrograms/g i.p., it significantly increased growth delay upon heat exposures of 15 min, but not after 30 or 60 min HT. Hydralazine at 10 micrograms/g i.p. increased growth delay for all heat doses (P less than 0.05). Hydralazine alone had no influence on growth delay of sham-heated tumors. The results obtained clearly indicate that tumor and normal tissues have microcirculatory differences in the time-course, degree and/or direction of response after hydralazine, and that hydralazine has potential for increasing the response of tumor to HT.
authors.affiliation: Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
authors.forename: J
authors.initials: J
authors.lastname: Kalmus
authors.forename: P
authors.initials: P
authors.lastname: Okunieff
authors.forename: P
authors.initials: P
authors.lastname: Vaupel
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology*; D006979:Hyperthermia, Induced; D007834:Lasers; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000503:physiopathology*
chemical_list: D006830:Hydralazine